In conclusion, a negative value of dTRX indicates a mutational impact whereby the stiffness of the DNA backbone in a given codon is decreased (i.e., flexibility increased), whereas a positive value indicates a stiffening of the DNA.
Our structure now provides a platform for the analysis of mutational impact on structure, ligand binding, and regulation of α-actinin in inherited human diseases (see Supplemental Information and Figure S7).
In this paper, we propose a practical approach that assesses mutational impact on pathway level mRNA expression.
Mutational impact assessment was done with the SIFT program [ 28, 29] using recommended best practices [ 28].
Interestingly, their highest mutational impact coincides with explorations of new adaptations by small subpopulations.
To further investigate the importance of mutational impacts on codon flexibility (dTRX) in driving common patterns observed in comparative genomics, we averaged the |dTRX| for the coding region of each gene and compared avg|dTRX| with Ts Tv ratios and levels of functional conservation on proteins (i.e., d N and d N/d S).
We investigated directly the potential role that codon assignments in the standard genetic code may play in biasing mutational impacts on DNA flexibility at the level of codons.
To assess potential influences of selective constraints on dTRX, we also included average random mutational impacts estimated from the real patterns of mutation in the yeast genomes as well.
These differences in average genomic mutational impacts on codons (dTRX) were highly significant (F = 646.23, num df = 5, denom df = 265, P < 0.0001; fig. 3 A).
Not surprisingly, comparative sequence analysis of the multiple alignments clearly indicated that the average mutational impacts of substitutions on the flexibility of codons (dTRX) were far greater, in those four substitution types which alter the local GC content.
